Is Direct Oral Anticoagulant (DOAC) monotherapy without aspirin effective for stroke risk reduction in patients with atrial fibrillation and stable Coronary Artery Disease (CAD)?

From the Guidelines

Direct Oral Anticoagulant (DOAC) monotherapy without aspirin is effective and recommended for stroke risk reduction in patients with atrial fibrillation and stable coronary artery disease. For patients with AF who have stable CAD, defined as no acute coronary events or revascularization for at least 12 months, DOAC monotherapy such as apixaban (5mg twice daily), rivaroxaban (20mg daily), dabigatran (150mg twice daily), or edoxaban (60mg daily) is appropriate without adding aspirin, as evidenced by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1. The use of DOACs has demonstrated advantages in stroke risk reduction compared to vitamin K antagonists (VKAs), with similar or improved bleeding rates, as seen in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials 1. Key points to consider include:

• The improved safety profile of DOACs leads to the recommendation to consider preferential use of a DOAC over a VKA 1.
• Adding aspirin to a DOAC in stable patients increases bleeding risk without providing additional benefit for stroke or cardiac event prevention.
• Dose adjustments may be necessary based on individual patient factors such as age, weight, and renal function.
• For patients who have recently undergone percutaneous coronary intervention or experienced an acute coronary syndrome within the past 12 months, a limited period of combined therapy (DOAC plus antiplatelet) may still be warranted before transitioning to DOAC monotherapy. The overall 19% reduction in stroke or systemic embolism, driven by a 51% reduction in hemorrhagic stroke and a 10% overall reduction in mortality, supports the use of DOAC monotherapy in this patient population 1.

From the Research

Efficacy of DOAC Monotherapy

• The study 2 found that DOACs had a lower risk of stroke/systemic embolism (OR, 0.64; 95% CI, 0.54-0.76, P < .00001) compared to warfarin in patients with stable coronary artery disease (CAD) and atrial fibrillation (AF).
• Another study 3 demonstrated that edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months compared to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001).
• The AFIRE trial 4 showed that rivaroxaban monotherapy was superior to combination therapy in terms of efficacy and safety endpoints in patients with atrial fibrillation and stable coronary artery disease who had previously undergone revascularisation.

Safety of DOAC Monotherapy

• The study 2 found that DOACs had a lower risk of intracranial bleeding (OR, 0.41; 95% CI, 0.26-0.64, P = .0001) and major bleeding (OR, 0.98; 95% CI, 0.81-1.148, P = .80) compared to warfarin.
• The study 3 demonstrated that edoxaban monotherapy led to a lower risk of major bleeding or clinically relevant nonmajor bleeding (hazard ratio, 0.34; 95% CI, 0.22 to 0.53) compared to dual antithrombotic therapy.
• The AFIRE trial 4 showed that rivaroxaban monotherapy had a lower risk of major bleeding (hazard ratio, 0.62; 95% CI: 0.39-0.98; p=0.042) compared to combination therapy in patients with atrial fibrillation and stable coronary artery disease who had previously undergone revascularisation.

Comparison with Other Therapies

• The study 5 found that rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority) and superior for the primary safety end point (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority) in patients with atrial fibrillation and stable coronary artery disease.
• The meta-analysis 6 found that dual antithrombotic treatments (DATs) including non-vitamin K antagonist oral anticoagulants (NOACs) and a P2Y12 inhibitor without aspirin were associated with significantly less bleeding than vitamin K antagonist (VKA)-based triple antithrombotic therapy (TAT) in atrial fibrillation patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI).